Background & Aims: The role of pre-treatment predictors of Interferon (IFN) response has been overshadowed by the strong predictive power of on-treatment viral kinetics. However, in recurrent hepatitis C (HCV) following liver transplantation, a strong negative pre-treatment predictor of IFN response would have the benefit of further optimizing response-guided therapy treatment algorithms while also positively impacting on patient selection to reduce IFN related risks. Methods: Consecutive patients with recurrent HCV treated with Ribavirin (Rbv) in combination with PegIFN or IFN, were tested for the IL28B rs12979860 SNP in DNA extracted from recipients blood sample and paraffin-embedded donor liver graft. Results: Out of the 110 HCV patients transplanted from 2000 to 2010, 54 (49%) received anti-HCV treatment and 48 completed post-treatment follow-up (37 males, median age 54 years, median donor age 57 years, 65% Cyclosporine A, 85% HCV 1-4, median HCVRNA 3.5 x106 UI/ml, 29% S≥4 by Ishak, median interval to treatment of 19 months, median treatment duration 45 weeks). The remaining 56 patients were not treated due to non progressive hepatitis (n=30), contraindications or severe co-morbidities (n=26). Overall an SVR was achieved in 56% of patients (49% genotype 1-4 vs. 100% genotype 2-3, p=0.01). The CC IL28B genotype was less common in recipient blood than in donor liver (24% vs 58%, p=0.001). In the 41 patients with genotype1-4, the donor CC IL-28B genotype had more SVR than CT/TT genotype (62% vs. 29%, p= 0.058), whereas this was not true for recipient IL-28B genotype (70% vs. 42%, p=0.15). Interestingly, when matching donor/recipient IL28B genotype, patients with either donor or recipient CC genotype had higher SVR rates than those without a CC (75% vs 20%, p=0.009). By multivariate logistic regression analysis in genotype 1-4, the presence of an IL28B CC genotype either in the donor or recipient (p=0.006; OR 11.7; 95% CI 2.05 - 66.55) and Cyclosporine A (p=0.03; OR 5.83; 95% CI 1.13 - 30) were independently associated with a SVR. Conclusion: Although the combination of donor/recipient IL28B genotype emerged as the strongest baseline predictor of treatment outcome its added value to the existing therapeutic algorithm is questionable in virtue of its unsatisfactory negative predictive power.
Donor/recipient match of IL28B to predict interferon response in recurrent hepatitis C
A. M. Aghemo
2011-01-01
Abstract
Background & Aims: The role of pre-treatment predictors of Interferon (IFN) response has been overshadowed by the strong predictive power of on-treatment viral kinetics. However, in recurrent hepatitis C (HCV) following liver transplantation, a strong negative pre-treatment predictor of IFN response would have the benefit of further optimizing response-guided therapy treatment algorithms while also positively impacting on patient selection to reduce IFN related risks. Methods: Consecutive patients with recurrent HCV treated with Ribavirin (Rbv) in combination with PegIFN or IFN, were tested for the IL28B rs12979860 SNP in DNA extracted from recipients blood sample and paraffin-embedded donor liver graft. Results: Out of the 110 HCV patients transplanted from 2000 to 2010, 54 (49%) received anti-HCV treatment and 48 completed post-treatment follow-up (37 males, median age 54 years, median donor age 57 years, 65% Cyclosporine A, 85% HCV 1-4, median HCVRNA 3.5 x106 UI/ml, 29% S≥4 by Ishak, median interval to treatment of 19 months, median treatment duration 45 weeks). The remaining 56 patients were not treated due to non progressive hepatitis (n=30), contraindications or severe co-morbidities (n=26). Overall an SVR was achieved in 56% of patients (49% genotype 1-4 vs. 100% genotype 2-3, p=0.01). The CC IL28B genotype was less common in recipient blood than in donor liver (24% vs 58%, p=0.001). In the 41 patients with genotype1-4, the donor CC IL-28B genotype had more SVR than CT/TT genotype (62% vs. 29%, p= 0.058), whereas this was not true for recipient IL-28B genotype (70% vs. 42%, p=0.15). Interestingly, when matching donor/recipient IL28B genotype, patients with either donor or recipient CC genotype had higher SVR rates than those without a CC (75% vs 20%, p=0.009). By multivariate logistic regression analysis in genotype 1-4, the presence of an IL28B CC genotype either in the donor or recipient (p=0.006; OR 11.7; 95% CI 2.05 - 66.55) and Cyclosporine A (p=0.03; OR 5.83; 95% CI 1.13 - 30) were independently associated with a SVR. Conclusion: Although the combination of donor/recipient IL28B genotype emerged as the strongest baseline predictor of treatment outcome its added value to the existing therapeutic algorithm is questionable in virtue of its unsatisfactory negative predictive power.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
